We propose to use two test systems to study cell-mediated cytotoxicity in Graves ophthalmopathy: 1) The lysis of lipid vesicles containing incorporated human eye muscle membrane protein (EMP) and intravesicular radioactive marker will be measured during incubation with peripheral blood lymphocytes from patients with Graves ophthalmopathy in the presence of added thyroglobulin (Tg) and Tg-anti Tg complex (TgA). 2) The lysis of cultured mouse L or C1 cells bearing fusion-induced incorporated eye muscle membrane and subsequently labelled with 111In-oxine will be measured under similar conditions. We will also perform studies on patients with Graves disease without ophthalmopathy, with other thyroid diseases, and with other eye diseases. Two-dimensional polyacrylamide gel electrophoresis will be used to separate individual protein components of EMP in an attempt to identify a specific component which is required for vesicle or cell lysis to occur under these defined conditions. We plan to study the time of origin, cause, duration, control and genetic association of T cell sensitization to thyroglobulin in patients with Graves ophthalmopathy.